Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism
Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism
复制标题
DOI：
10.1073/pnas.1016217108
复制
发表时间：
2011-04-19
影响因子：
11.1
通讯作者：
Kobayashi, Michihiko
中科院分区：
文献类型：
--
作者：
Hassaninasab, Azam;Hashimoto, Yoshiteru;Kobayashi, Michihiko
多酚姜黄素是一种黄色色素，来源于植物（姜黄）的根茎，是一种天然抗氧化剂，具有多种药理活性和治疗特性。长期以来，它一直被用作传统药物和食品中的防腐剂和着色剂。在这里，从人类粪便中分离出姜黄素转化微生物，其中表现出最高活性的微生物被鉴定为大肠杆菌。因此，我们是独一无二的发现，E。coli能够作用于姜黄素。从E.大肠杆菌中表达，并进行了表征。天然酶的分子量约为82 kDa，由两个相同的亚基组成。该酶具有窄的底物谱，优先作用于姜黄素。姜黄素的微生物代谢的纯化的酶被发现，包括两步还原，姜黄素被转化成NADPH依赖性的中间产物，二氢姜黄素，然后最终产品，四氢姜黄素。我们将这种酶命名为“NADPH依赖性姜黄素/二氢姜黄素还原酶”（CurA）。还鉴定了编码该酶的基因（curA）。同源性搜索与BLAST程序显示，一个独特的酶参与姜黄素代谢属于中链脱氢酶/还原酶超家族。
Polyphenol curcumin, a yellow pigment, derived from the rhizomes of a plant (Curcuma longa Linn) is a natural antioxidant exhibiting a variety of pharmacological activities and therapeutic properties. It has long been used as a traditional medicine and as a preservative and coloring agent in foods. Here, curcumin-converting microorganisms were isolated from human feces, the one exhibiting the highest activity being identified as Escherichia coli. We are thus unique in discovering that E. coli was able to act on curcumin. The curcumin-converting enzyme was purified from E. coli and characterized. The native enzyme had a molecular mass of about 82 kDa and consisted of two identical subunits. The enzyme has a narrow substrate spectrum, preferentially acting on curcumin. The microbial metabolism of curcumin by the purified enzyme was found to comprise a two-step reduction, curcumin being converted NADPH-dependently into an intermediate product, dihydrocurcumin, and then the end product, tetrahydrocurcumin. We named this enzyme "NADPH-dependent curcumin/dihydrocurcumin reductase" (CurA). The gene (curA) encoding this enzyme was also identified. A homology search with the BLAST program revealed that a unique enzyme involved in curcumin metabolism belongs to the medium-chain dehydrogenase/reductase superfamily.